Fe(NO3)3/2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ): An efficient catalyst system for selective oxidation of alcohols under aerobic conditions

Article abstract of DOI:10.1016/j.catcom.2017.09.019

A practical and efficient catalyst system for the oxidation of alcohols to carbonyl compounds using catalytic amounts of DDQ and Fe(NO₃)₃ with air as the environmentally benign oxidant has been developed. A variety of benzylic, heterocyclic, allylic and propargylic alcohols were smoothly converted into aldehydes or ketones in good to excellent yields. In case of large-scale reaction for the oxidation of benzyl alcohol, benzaldehyde was obtained in 93% isolated yield. Moreover, a possible reaction mechanism was proposed.

Full text of DOI:10.1016/j.catcom.2017.09.019

Accepted Manuscript
Fe(NO3)3/2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ):
An efficient catalyst system for selective oxidation of alcohols
under aerobic conditions
Yongke Hu, Lei Chen, Bindong Li
PII:
S1566-7367(17)30392-8
doi:10.1016/j.catcom.2017.09.019
CATCOM 5201
DOI:
Reference:
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
12 July 2017
18 September 2017
20 September 2017
Please cite this article as: Yongke Hu, Lei Chen, Bindong Li , Fe(NO3)3/
,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ): An efficient catalyst system for
2
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ACCEPTED MANUSCRIPT
Fe(NO
3
)
3
/2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ): An efficient Catalyst System for
Selective Oxidation of Alcohols under Aerobic Conditions
Yongke Hu, Lei Chen, Bindong Li*
School of Chemical Engineering, Nanjing University of Science and Technology,
Nanjing 210094, PR China
E-mail: libindong@njust.edu.cn
Abstract
A practical and efficient catalyst system for the oxidation of alcohols to carbonyl
compounds using catalytic amounts of DDQ and Fe(NO3)3 with air as the
environmentally benign oxidant has been developed. A variety of benzylic,
heterocyclic, allylic and propargylic alcohols were smoothly converted into aldehydes
or ketones in good to excellent yields. In case of large-scale reaction for the oxidation
of benzyl alcohol, benzaldehyde was obtained in 93% isolated yield. Moreover, a
possible reaction mechanism was proposed.
Introduction
The selective oxidation of alcohols into corresponding aldehydes or ketones is a
fundamental transformation in organic chemistry and the carbonyl compounds are
widely used as important precursors for pharmaceuticals, perfumes and organic
intermediates [1, 2]. Traditional methods for this transformation involve the use of
stoichiometric amount of oxidants such as MnO2 [3], chromium oxides [4], activated
DMSO [5] and hypervalent iodine [6], which produce large amounts of toxic waste
and cause pollution to the environment. From the viewpoints of green and sustainable
chemistry, molecular oxygen as a green oxidant has attracted great attention because
molecular oxygen is inexpensive, abundant and water is produced as the only
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innocuous by-product [7, 8]. Thus, considerable efforts have been devoted to
developing green and facile approaches for the oxidation of alcohols with molecular
oxygen as the terminal oxidant. Over the past decades, numerous protocols have been
developed and showed high efficiency in aerobic alcohol oxidation with transition
metal catalysts or metal-free catalysts [9, 10]. Among all the catalytic system the ones
based on stable nitroxyl radical such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)
and N-hydroxyphthalimide (NHPI) in combination with co-catalysts are the most
reported [11-14].
In recent years, a new organocatalyst, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ) has been recognized as an powerful oxidant for numerous organic
transformation [15]. Although DDQ is efficient for alcohol oxidation [16],
aromatization [17], oxidative cyclization [18] and deprotection [19], stoichiometric or
even excess amounts of DDQ are required. In addition, the stoichiometric use of DDQ
produces equimolar quantities of the corresponding hydroquinone (DDQH2)
byproduct, which makes purification difficulties on the large scale synthesis. To date,
few works have been reported for the alcohol oxidation using substoichiometric
quantities of DDQ. Helquist and co-workers described a practical, chemoselective
method for the oxidation of alcohols by employing 20 mol% of DDQ as the oxidant
and 6 equiv of Mn(OAc)3 as the co-oxidant (Scheme 1, a) [20]. However, the use of
excess amounts of Mn(OAc)3 made this protocol environmentally unfriendly. Gao and
co-workers developed a transition-metal-free catalytic system by using low catalytic
amount of DDQ and NaNO2 with molecular oxygen as terminal oxidant, but this
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catalytic system was limited for the oxidation of benzylic alcohols containing
electron-withdrawing groups (Scheme 1, b) [21]. Subsequently, Moody and
co-workers reported a similar catalyst system with catalytic amount of DDQ and
NaNO2 or tert-butyl nitrite under visible light irradiation (Scheme 1, c) [22]. Both
Gao’s and Moody’s work were nitrite-based protocols, the sodium nitrite was
employed as co-catalyst and AcOH was also required. In the presence of AcOH and
oxygen, nitric oxide was generated in suit by sodium nitrite, which was a sufficiently
strong oxidant to recycle the DDQH2. As we know, DDQH2 cannot be directly
oxidized to DDQ by molecule oxygen in the absence of co-catalyst under mild
conditions. Hence, the development of an efficient and inexpensive co-catalyst in
combination with catalytic amount of DDQ for the aerobic oxidation of alcohols
under mild conditions is still highly desired.
Iron, a cheap, non-toxic, and earth-abundant metal, has been developed as a catalyst
for many organic reactions, especially in some oxidation reactions using oxygen as
oxidant [23]. The mainly catalytic systems were based on TEMPO in combination
with Fe salts as the co-catalyst. In 2005, Wang et al. first reported FeCl3/TEMPO/
NaNO2 catalyst system for the alcohol oxidation [24]. Further developments of the
Fe(NO3)3/TEMPO catalyst system were reported by Ma et al. and Fe(NO3)3 was
proven to be an efficient and promising catalyst for the alcohol oxidation (Scheme 1,
d) [25-28]. Therefore, we hypothesized Fe(NO3)3 has a potential as good co-catalyst
in DDQ catalytic system for the oxidation of alcohols.
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Herein, we wish to report a facile and efficient approach for the oxidation of alcohols
to carbonyl compounds by using catalytic amount of DDQ as catalyst, cheap and
nontoxic Fe(NO ) as the co-catalyst and air as the terminal oxidant (Scheme 1, e). A
3
3
variety of aldehydes and ketones were obtained in moderate to excellent yields.
Result and discussion
Initially, benzyl alcohol (1a) was employed as model substrate to optimize reaction
conditions including catalysts, solvents and reaction time under air. As shown in Table
1
, different iron catalysts such as Fe2(SO4)3, FeCl3, FeCl2, Fe(acac)3 and Fe(NO3)3
o
were screened in the present of 3 mol% DDQ at 60 C under air balloon (Table 1,
entries 1-5). To our delight, Fe(NO3)3 showed higher catalytic activity than other iron
salts and product 2a was isolated in 80% yield (Table 1, entry 5). Next, the influence
of the catalyst loading and reaction time on the reaction was investigated. It was
found that 3 h and 10 mol% of Fe(NO ) , 5 mol% of DDQ were sufficient for this
3
3
transformation (Table 1, entries 6-9). Among all the solvents screened,
,2-dichloroethane gave the best result compared with other solvents such as toluene,
1
CH3OH, CH2Cl2 and H2O (Table 1, entries 10-13). In addition, we attempted different
o
reaction temperatures, and 60 C was the better choice (Table 1, entries 14 and 15).
o
Therefore, we chose 10 mol% Fe(NO3)3, 5 mol% DDQ in 1,2-dichloroethane at 60 C
under air as the standard reaction conditions (Table 1, entry 7).
With the optimal reaction condition in hand, the substrate scope and limitation of this
catalytic system were examined. Firstly, we investigated the oxidation of a variety of
primary alcohols under standard conditions. To our delights, both electron-donating
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groups and electron-withdrawing groups were well tolerated in the reactions. It was
observed that benzylic alcohols bearing electron-donating groups were fully
converted to the desired products (Table 2, 2b-2g). However, the
electron-withdrawing groups such as -F, Br, -Cl, -NO2 and -CF3 substituted benzylic
alcohols provided slightly low yields of corresponding aldehydes (Table 2, 2h-2m).
Notably, 4-chlorobenzylalcohol and 4-nitrobenzylalcohol were smoothly transformed
to the desired products, which was superior to the previous works reported by Gao’s
and Helquist’s group. Benzyl alcohols with methylthiol and hydroxyl substitution
gave the corresponding products in 93% and 74% yields, which indicated that
methylthiol and hydroxyl substitution on the phenyl group was unaffected under the
standard reaction conditions (Table 2, 2n and 2o). For the piperonyl alcohol,
4
-phenylbenzyl alcohol and 1-naphthalenemethanol, they were oxidized to the desired
products in moderate to good yields (Table 2, 2p-2r). In the case of unsaturated
alcohols such as cinnamyl alcohol, α-methylcinnamyl alcohol and
3
-phenylprop-2-yn-1-ol were also well tolerated in this reaction (Table 2, 2s-2u). In
addition, heterocyclic alcohols such as 2-furanemethanol and 2-thiophenemethanol
were tested successively and transformed smoothly with acceptable yields (Table 2,
2
v-2w).
The oxidation of secondary alcohols was also tested and the results were summarized
in Table 3. As expected, all secondary benzylic alcohols were converted into
corresponding ketones in moderate to high yields (Table 3, 4a-4p). It was worthy to
note that when the length of the side chain increasing, the products yield reduced,
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which indicated that the steric hindrance of the groups on the side chain had an
obvious impact on this transformation (Table 3, 4a-4c). Similarly, the reaction activity
decreased, when the size of the ring on the side of the hydroxyl enlarging (Table 3,
4
i-4k). In addition, it was found that secondary propargylic alcohols such as
1
-phenylprop-2-yn-1-ol and 1-phenyl-1-pentyn-3-ol were also smoothly oxidized to
the desired ketones with good yields (Table 3, 4o and 4p). Unfortunately, both
primary and secondary aliphatic alcohols were failed to afford the desired products
under standard conditions (Table 2, 2x and Table 3, 4q). The important advantage of
this catalytic system is that the use of air as the terminal oxidant instead of pure
dioxygen also results in good yields.
To further confirm the practicality and efficiency of this catalyst system, a
large-scale experiment for the oxidation of 1a was conducted under standard
conditions. Product of 2a was successfully obtained in 93% isolated yield (Scheme 2).
The result suggested that this catalyst system was amenable to scale up.
In order to explore the reaction mechanism, the following control experiments were
carried out and the results were illustrated in Scheme 3. When the reaction was
conducted in the presence of NaNO3 or FeCl3·6H2O, only 10% and 29% yield of
benzaldehyde was isolated, respectively. Besides, the yield of benzaldehyde increased
to 76% by employing 30 mol% NaNO3 combined with 10 mol% FeCl3·6H2O in the
3
+
-
reaction. These results indicated that Fe as well as NO3 was essential in this
3
+
2+
reaction. Additionally, we considered that the Fe can be transformed into Fe in the
process of oxidation. In order to demonstrate the metal chemical state, a small
6

ACCEPTED MANUSCRIPT
quantity of the reaction mixture was added discontinuously to the K3[Fe(CN)6]
solution. The Prussian blue precipitate appeared rapidly and existed throughout the
aerobic oxidation of benzyl alcohol even after the completion of the reaction, which
2
+
indicated the generation of Fe during the reaction. However, when the reaction
mixture was in the absence of DDQ, the Prussian blue precipitate was not obtained.
Based on the results above and pertinent literature [25, 29-31], a plausible mechanism
for the oxidation of alcohols catalyzed by Fe(NO3)3/DDQ was presented in Scheme 4.
Firstly, DDQ oxidized alcohols to carbonyl compounds and itself was converted to
3
+
2+
-
DDQH2. Then DDQH2 reduced the Fe to Fe . The NO3 was to be a source of NO2,
2
+
3+
-
which played an important role in the oxidation of Fe to Fe and then NO3 was
-
-
reduced to NO2 [32-35]. Finally, NO3 could be easily regenerated by the oxidation of
-
NO2 with molecular oxygen.
Conclusion
In summary, we have developed a highly efficient Fe(NO3)3/DDQ-catalyzed system
for the oxidation of alcohols with air serving as the environmentally friendly terminal
oxidant. This catalytic system exhibits excellent substrate tolerance and a variety of
benzylic, heterocyclic, allylic and propargylic alcohols are selectively transformed to
the corresponding aldehydes and ketones in moderate to good yields. In addition, a
plausible reaction mechanism has been proposed and further applications of this
catalytic system are under way in our laboratory.
References
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1
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1
0

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Scheme 1. Methods for the oxidation of alcohols with DDQ
Scheme 2. Aldehyde formation in the large-scale.
Scheme 3. Control experiments.
11

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Scheme 4. Proposed reaction mechanism.
1
2

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a
Table 1. Optimization of reaction conditions
Fe catalyst
DDQ
(mol %)
Time
(h)
4
c
Entry
Solvent
Yield (%)
b
(mol %)
1
2
3
4
5
6
7
8
9
Fe2(SO4)3·9H2O (5)
FeCl ·6H O (5)
3
3
3
3
3
5
5
10
5
5
5
5
5
5
5
DCE
DCE
16
25
18
12
80
91
98
98
89
75
69
92
20
96
90
4
3
2
FeCl2·4H2O (5)
Fe(acac)3 (5)
Fe(NO3)3 (5)
Fe(NO3)3 (5)
Fe(NO ) (10)
DCE
4
DCE
4
DCE
4
DCE
4
DCE
DCE
3
3
3
Fe(NO3)3 (15)
Fe(NO3)3 (10)
Fe(NO3)3 (10)
Fe(NO3)3 (10)
Fe(NO ) (10)
3
DCE
2
1
0
Toluene
MeOH
CH Cl
3
11
3
1
1
2
3
3
3
3
2
2
Fe(NO3)3 (10)
Fe(NO3)3 (10)
Fe(NO3)3(10)
H2O
3
d
14
DCE
DCE
3
e
15
3
a
Reaction condition: 1a (1 mmol), Fe catalyst, DDQ, solvent (2 mL) in a 10 mL
b
Schlenk tube, at 60 °C, under air balloon. Fe(NO ) = Fe(NO ) ·9H O unless
otherwise noted. Isolated yield. Reaction at 65 °C Reaction at 55 °C
3
3
3 3
2
c
d
e
1
3

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Table 2. Aerobic oxidation of primary alcohols to aldehydes catalyzed by
a
DDQ/Fe(NO3)3
a
Reaction conditions: 1 (1 mmol), Fe (NO3)3 (10 mol%), DDQ (5 mol%), DCE (2 mL)
in a 10 mL Schlenk tube, at 60 °C for 3 h, under air balloon. Isolated yield.
1
4

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Table 3. Aerobic oxidation of secondary alcohols to ketones catalyzed by
a
DDQ/Fe(NO3)3
a
Reaction conditions: 1 (1 mmol), Fe (NO ) (10 mol%), DDQ (5 mol%), DCE (2 mL)
3
3
in a 10 mL Schlenk tube, at 60 °C for 3 h, under air balloon. Isolated yield.
1
5

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Highlights
·
·
·
Fe(NO3)3 and DDQ as the catalysts with air as the terminal oxidant.
Various aldehydes and ketones were obtained in good to excellent yields.
A plausible mechanism was proposed.
1
6